EvoMining
Nelly Selem
December31, 2017
EvoMining 2.0: A customizable computational pipeline for evolutionary reconstructions during genome mining
Selem-Mojica Nelly, Cruz-Morales Pablo, Martínez-Guerrero Christian , …, and Barona-Gómez Francisco
Abstract
Microbial natural products has importance in human health and life. Due to the abundance of genomic and metagenomic data, new natural products research by genome mining is a growing field. Traditional genome mining approaches explored bacterial genomes localizing marks of previously knwon secondary metabolism enzymes organized on biosynthetic gene clusters (BGCs). Here we present EvoMining a downloadable visual genome mining tool that incorporates evolution theory into genome mining. On EvoMining databases are customizable, its based on enzyme expansions not on BGCs. The advantage of this method is that every expanded enzyme family is a candidate to explore recruitments, and all prokatyiotic genome, even the unexplored Archaea kingdom. On this study EvoMining was applied to several database such as Cyanobacteria, Actinobacteria, Pseudomonas and Archea studying expansions for enzyme families such as TauD and other enzymes recently recruited onto secondary metabolism. Finally the genomic plasticity of Streptomyces coelicolor known BGCs i explored generlizind applying the open/Close pangenome approach to a BGCs. This Evolutionary methods open the door to discover not previously knwon chemical compounds at private genome collections and prioritize them according to their genomic plasticity.
Introduction
Natural products are synthesized by biosynthetical gene clusters (BGCs) codified on the genome of a wide range of microorganisms. Enzymes that belong to a BGC can either be mainly restricted to secondary metabolism, or be a recent recruitment acting as accesory enzymes.
With the genomic era and 500,000 prokaryotic genomes available at NCBI, there has been a oom of development of specilized genome mining software. Traditional approaches are based on recognize marks of enzymes devoted to secondary metabolism (???), or domains (???) lattely Evolution (??? nadine).
On prokaryotic genomes enzyme families are expanded frequently either by duplication or by horizontal gene transfer and that this expansions are acting as evolutionary raw material being recruited into secondary metabolism to perform nobel chemical functionalities. A proof of concept of EvoMining idea was provided by the discovery of an arseno compound on Streptomyces coelicolor (Cruz-Morales et al. 2016), nevertheless.
Despite EvoMining analysis has recently being present on the natural products field (Blin et al. 2017,Alanjary et al. (2017),Ziemert, Alanjary, and Weber (2016),Miller, Chevrette, and Kwan (2017)) EvoMining software has not been released, on this work we free EvoMining as a downloadable stand alone tool implemented on a docker container. EvoMining is free and open to all users and there is no login requirement. Despite Actinobacteria are great natural product producers (???) other microrganisms can be explored.
Here we present the EvoMining expansions analysis using different genome-DB such as Actinobacteria, Cyanobacteria, Pseudomonas and Archaea. To enrich possibilities of central DB an example of what we called backward EvoMining was incorporated: BGCs from S coelicolor available at Mi-BIG were analyzed EvoMining backwards and all enzyme families expanded but not over represented were followed.
Finally to prioritize which clusters possess more metabolite variations, assuming a link between genomic and metabolite plasticity we introduce the idea of classifying the saturation of a pangenome as open/closed pangenome measuring BGCs as open / closed BGC.
table <- read.csv("Figura3MiBIG/CoelicolorMiBIG", row.names = 1,sep="\t")
kable(table, caption = "Coelicolor\\label{tab:Coelicolor MiBig}",caption.short = "CoelicolorMiBig ")| Full…partial | Main.product | Biosynthetic.class | Organism | X..Backward.EvoMining.Hits | Open.closed | |
|---|---|---|---|---|---|---|
| BGC0000038 | Full | coelimycin | Polyketide | Streptomyces coelicolor A3(2) | NA | NA |
| BGC0000194 | Full | actinorhodin | Polyketide | Streptomyces coelicolor A3(2) | NA | NA |
| GC0000315 | Full | calcium-dependent antibiotic | NRP | Streptomyces coelicolor A3(2) | NA | NA |
| BGC0000551 | Full | sapB | RiPP | Streptomyces coelicolor A3(2) | NA | NA |
| BGC0000595 | Full | SCO-2138 | RiPP | Streptomyces coelicolor A3(2) | NA | NA |
| BGC0000849 | Full | gamma-butyrolactone | Other | Streptomyces coelicolor A3(2) | NA | NA |
| BGC0000940 | Full | desferrioxamine B | Other | Streptomyces coelicolor A3(2) | NA | NA |
| BGC0000324 | Partial | coelibactin | NRP | Streptomyces coelicolor A3(2) | NA | NA |
| BGC0000325 | Partial | coelichelin | NRP | Streptomyces coelicolor A3(2) | NA | NA |
| BGC0000660 | Partial | albaflavenone | Terpene | Streptomyces coelicolor A3(2) | NA | NA |
| BGC0000663 | Partial | hopene | Terpene | Streptomyces coelicolor A3(2) | NA | NA |
| BGC0000910 | Partial | melanin | Other | Streptomyces coelicolor A3(2) | NA | NA |
| BGC0000914 | Partial | methylenomycin | Other | Streptomyces coelicolor A3(2) | NA | NA |
| BGC0001063 | Partial | undecylprodigiosin | NRP / Polyketide | Streptomyces coelicolor A3(2) | NA | NA |
| BGC0001181 | Partial | geosmin | Terpene | Streptomyces coelicolor A3(2) | NA | NA |
| ## Results a | nd Discussion |
Figure 1 EvoMining pipe-line
EvoMining is a visual, evolutionary based genome mining tool with the milestone of prioritize non standard secondary metabolite pathways. The algorithm follows enzyme families from central pathways on their recruitment as components of natural products biosynthetic gene clusters (BGCs) within a genomic database.
Pipeline
EvoMining inputs are a (1) a custom genomic database (genomic-DB), (2) a central pathways database (central-DB) and (3) a natural product database (natural-DB) composed of genes that belongs to experimentally tested BGCs. These three databases are provided and can be modified, replaced and expanded by the user. In this work genomic-DB are collection of up to date genomes in RAST format from taxonomically related organisms such as Actinobacteria, Cyanobacteria, Pseudomonas and Archaea. Selection of this taxa obeys to the possibility of comparing well known NPs producing organisms such as Actinobacteria and Cyanobacteria in contrast with Archaea that has been poorly investigated. The central-DB contains nine central pathways from Actinobacteria previously curated (Barona-Gómez, Cruz-Morales, and Noda-García 2012), plus an update of seed metabolic enzymes identified after manual curation congruent with the central EvoMining paradigm. The natural-DB currently comprises all sequences that belongs to some BGCs from The Minimum Information about a Biosynthetic Gene cluster (MIBiG) (Medema et al. 2015).
As output EvoMining identifies on the genomic-DB those expanded families from the central-DB that has at least a recruited member onto the natural-DB, proceeding then to the reconstruction of the evolutionary history of the enzyme family. Given an enzyme from the central-DB, the product of EvoMining analysis is a color coded tree of the expanded enzyme family that provides information about the metabolic fate. Specifically, enzymes from central metabolism are differentiated from known Natural Products enzymes and those expansions with potential activity into secondary metabolism are emphasised as putative novel recruitments. Further analysis of these hits allows visualization of the genomic vicinity guiding to the discovery of novel BGCs. In addition to the updates associated to the workflow of EvoMining, the version to be released will include the possibility of defining the dynamics of the gene content of any given BGC to explore the chemical plasticity related to EvoMining hits. This allows to prioritize which clusters possess more metabolite variations, therefore unmasking biosynthetic darkmatter (Medema and Fischbach 2015, Blin et al. 2017).
EvoMining code and components (blast, muscle, FastTree, newick utilities, Gblocks,apache and SVG perl module) are wrapped on the docker container nselem/newevomining downloadable at the Docker hub. Code is available at at github: nselem/EvoMining and manual at https://github.com/nselem/EvoMining/wiki. EvoMining tool will allow researchers to examine their own genomes and their own enzyme families in the search of expansions involved on nobel secondary metabolism.
EvoMining will identify those expanded families of the central-DB within the genomic-DB that has at least a recruited member onto the natural-DB, proceeding then to the reconstruction of the evolutionary history of the enzyme family. Given an enzyme from the central-DB, the product of EvoMining analysis is an interactive color coded tree of the enzyme expanded family where best bidirectional hits (BBH) of central-DB are differentiated from Natural Products members and those expansions close to a Natural Product sequence that are not BBH with central-DB enzymes are emphasised as putative nobel recruitments into secondary metabolism.
Figure 2 Expansions on some databases
Archaea Cyanobacteria, and Actinobacteria based on central metabolism from actinobacteria
To acotate the search for enzymes of recent recruitment into natural products 
### Figure 3.1 Expansions on genomic dinamics
3.2(Bakward EvoMining)
Coelicolor clusters
tableExp <- read.csv("Figura3MiBIG/ExpansionBlast.data", row.names = 1,sep="\t")
kable(tableExp, caption = "CoelicolorExpansions\\label{tab:Coelicolor Expansions}",caption.short = "CoelicolorExpansions")| Copies | OrganismPercentage | Organismos | Expansions | ExpOverOrg | ExpNum | Function | |
|---|---|---|---|---|---|---|---|
| actinorhodin|6|74_1|Scoe | 636 | 0.2663212 | 514 | 122 | 1.237354 | 0.1918239 | hydroxylacyl-CoA dehydrogenase |
| actinorhodin|6|75_1|Scoe | 10884 | 0.8937824 | 1725 | 9159 | 6.309565 | 0.8415105 | 3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.35) |
| actinorhodin|6|76_1|Scoe | 20061 | 0.9082902 | 1753 | 18308 | 11.443811 | 0.9126165 | FIG01127617: hypothetical protein |
| actinorhodin|6|77_1|Scoe | 196 | 0.0963731 | 186 | 10 | 1.053763 | 0.0510204 | hypothetical protein |
| actinorhodin|6|78_1|Scoe | 20077 | 0.9098446 | 1756 | 18321 | 11.433371 | 0.9125367 | Bifunctional protein: zinc-containing alcohol dehydrogenase; quinone oxidoreductase ( NADPH:quinone reductase) (EC 1.1.1.-); Similar to arginate lyase |
| actinorhodin|6|79_1|Scoe | 20002 | 0.9093264 | 1755 | 18247 | 11.397151 | 0.9122588 | putative integral membrane protein |
| actinorhodin|6|80_1|Scoe | 756 | 0.3015544 | 582 | 174 | 1.298969 | 0.2301587 | hypothetical protein |
| actinorhodin|6|81_1|Scoe | 125 | 0.0507772 | 98 | 27 | 1.275510 | 0.2160000 | FIG01121294: hypothetical protein |
| actinorhodin|6|82_1|Scoe | 3722 | 0.7388601 | 1426 | 2296 | 2.610098 | 0.6168726 | FIG01124094: hypothetical protein |
| actinorhodin|6|83_1|Scoe | 3473 | 0.6191710 | 1195 | 2278 | 2.906276 | 0.6559171 | Acyl-CoA dehydrogenase |
| actinorhodin|6|84_1|Scoe | 614 | 0.2487047 | 480 | 134 | 1.279167 | 0.2182410 | FIG01134414: hypothetical protein |
| actinorhodin|6|85_1|Scoe | 14217 | 0.8829016 | 1704 | 12513 | 8.343310 | 0.8801435 | Transcriptional regulator, TetR family |
| actinorhodin|6|86_1|Scoe | 20004 | 0.9098446 | 1756 | 18248 | 11.391799 | 0.9122176 | FIG01129015: hypothetical protein |
| actinorhodin|6|87_1|Scoe | 13480 | 0.9202073 | 1776 | 11704 | 7.590090 | 0.8682493 | Hopanoid-associated RND transporter, HpnN |
| actinorhodin|6|88_1|Scoe | 17061 | 0.8191710 | 1581 | 15480 | 10.791271 | 0.9073325 | actinorhodin cluster activator protein |
| actinorhodin|6|89_1|Scoe | 20000 | 0.9492228 | 1832 | 18168 | 10.917031 | 0.9084000 | Short-chain dehydrogenase/reductase SDR |
| actinorhodin|6|90_1|Scoe | 25875 | 0.9145078 | 1765 | 24110 | 14.660057 | 0.9317874 | Polyketide beta-ketoacyl synthase WhiE-KS paralog |
| actinorhodin|6|91_1|Scoe | 25118 | 0.9139896 | 1764 | 23354 | 14.239229 | 0.9297715 | Polyketide chain length factor WhiE-CLF paralog |
| actinorhodin|6|92_1|Scoe | 1728 | 0.5549223 | 1071 | 657 | 1.613445 | 0.3802083 | Acyl carrier protein |
| actinorhodin|6|93_1|Scoe | 1729 | 0.5569948 | 1075 | 654 | 1.608372 | 0.3782533 | actinorhodin polyketide synthase bifunctional cyclase/dehydratase |
| actinorhodin|6|94_1|Scoe | 3237 | 0.7668394 | 1480 | 1757 | 2.187162 | 0.5427865 | putative polyketide cyclase |
| actinorhodin|6|95_1|Scoe | 7433 | 0.8518135 | 1644 | 5789 | 4.521289 | 0.7788242 | NADH-FMN oxidoreductase |
| albaflavenone|7|96_1|Scoe | 3313 | 0.6005181 | 1159 | 2154 | 2.858499 | 0.6501660 | FIG00456465: hypothetical protein |
| albaflavenone|7|97_1|Scoe | 15775 | 0.8538860 | 1648 | 14127 | 9.572209 | 0.8955309 | putative cytochrome P450 |
| calcium-dependent_antibiotic|4|23_1|Scoe | 2914 | 0.9217617 | 1779 | 1135 | 1.637999 | 0.3894990 | 2-keto-3-deoxy-D-arabino-heptulosonate-7-phosphate synthase II (EC 2.5.1.54) |
| calcium-dependent_antibiotic|4|24_1|Scoe | 2198 | 0.9445596 | 1823 | 375 | 1.205705 | 0.1706096 | Indole-3-glycerol phosphate synthase (EC 4.1.1.48) |
| calcium-dependent_antibiotic|4|25_1|Scoe | 2139 | 0.9150259 | 1766 | 373 | 1.211212 | 0.1743806 | Anthranilate phosphoribosyltransferase (EC 2.4.2.18) |
| calcium-dependent_antibiotic|4|26_1|Scoe | 6890 | 0.9829016 | 1897 | 4993 | 3.632051 | 0.7246734 | Anthranilate synthase, amidotransferase component (EC 4.1.3.27) |
| calcium-dependent_antibiotic|4|27_1|Scoe | 7434 | 0.9626943 | 1858 | 5576 | 4.001076 | 0.7500673 | Anthranilate synthase, aminase component (EC 4.1.3.27) |
| calcium-dependent_antibiotic|4|28_1|Scoe | 149 | 0.0766839 | 148 | 1 | 1.006757 | 0.0067114 | hypothetical protein |
| calcium-dependent_antibiotic|4|29_1|Scoe | 12084 | 0.9787565 | 1889 | 10195 | 6.397036 | 0.8436776 | Cation-transporting ATPase, E1-E2 family |
| calcium-dependent_antibiotic|4|30_1|Scoe | 20684 | 0.8082902 | 1560 | 19124 | 13.258974 | 0.9245794 | FIG01132787: hypothetical protein |
| calcium-dependent_antibiotic|4|31_1|Scoe | 4960 | 0.7849741 | 1515 | 3445 | 3.273927 | 0.6945565 | Polymyxin synthetase PmxB |
| calcium-dependent_antibiotic|4|32_1|Scoe | 2216 | 0.5440415 | 1050 | 1166 | 2.110476 | 0.5261733 | putative lipase (putative secreted protein) |
| calcium-dependent_antibiotic|4|33_1|Scoe | 40 | 0.0165803 | 32 | 8 | 1.250000 | 0.2000000 | putative secreted protein |
| calcium-dependent_antibiotic|4|34_1|Scoe | 2082 | 0.8953368 | 1728 | 354 | 1.204861 | 0.1700288 | Arogenate dehydrogenase (EC 1.3.1.43) |
| calcium-dependent_antibiotic|4|35_1|Scoe | 877 | 0.3725389 | 719 | 158 | 1.219750 | 0.1801596 | secreted protein |
| calcium-dependent_antibiotic|4|36_1|Scoe | 4941 | 0.8139896 | 1571 | 3370 | 3.145131 | 0.6820482 | Thiamin ABC transporter, transmembrane component |
| calcium-dependent_antibiotic|4|37_1|Scoe | 20006 | 0.9772021 | 1886 | 18120 | 10.607635 | 0.9057283 | putative ABC transporter ATP-binding protein |
| calcium-dependent_antibiotic|4|38_1|Scoe | 20150 | 0.8663212 | 1672 | 18478 | 12.051435 | 0.9170223 | two component sensor kinase |
| calcium-dependent_antibiotic|4|39_1|Scoe | 20000 | 0.8808290 | 1700 | 18300 | 11.764706 | 0.9150000 | DNA-binding response regulator, LuxR family |
| calcium-dependent_antibiotic|4|40_1|Scoe | 8235 | 0.9487047 | 1831 | 6404 | 4.497542 | 0.7776563 | putative aminotransferase |
| calcium-dependent_antibiotic|4|41_1|Scoe | 2983 | 0.7601036 | 1467 | 1516 | 2.033402 | 0.5082132 | (S)-2-hydroxy-acid oxidase (EC 1.1.3.15) |
| calcium-dependent_antibiotic|4|42_1|Scoe | 3205 | 0.7953368 | 1535 | 1670 | 2.087948 | 0.5210608 | 4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27) |
| calcium-dependent_antibiotic|4|43_1|Scoe | 197580 | 0.8176166 | 1578 | 196002 | 125.209125 | 0.9920134 | Siderophore biosynthesis non-ribosomal peptide synthetase modules @ Bacillibactin synthetase component F (EC 2.7.7.-) |
| calcium-dependent_antibiotic|4|44_1|Scoe | 87847 | 0.8186528 | 1580 | 86267 | 55.599367 | 0.9820142 | Siderophore biosynthesis non-ribosomal peptide synthetase modules @ Bacillibactin synthetase component F (EC 2.7.7.-) |
| calcium-dependent_antibiotic|4|45_1|Scoe | 63839 | 0.8186528 | 1580 | 62259 | 40.404430 | 0.9752502 | Siderophore biosynthesis non-ribosomal peptide synthetase modules @ Bacillibactin synthetase component F (EC 2.7.7.-) |
| calcium-dependent_antibiotic|4|46_1|Scoe | 13271 | 0.8968912 | 1731 | 11540 | 7.666667 | 0.8695652 | Beta-ketoadipate enol-lactone hydrolase (EC 3.1.1.24) |
| calcium-dependent_antibiotic|4|47_1|Scoe | 1043 | 0.5124352 | 989 | 54 | 1.054601 | 0.0517737 | phosphotransferase |
| calcium-dependent_antibiotic|4|48_1|Scoe | 21541 | 0.9782383 | 1888 | 19653 | 11.409428 | 0.9123532 | ABC transporter, NBP/MSD fusion protein |
| calcium-dependent_antibiotic|4|49_1|Scoe | 1165 | 0.3901554 | 753 | 412 | 1.547145 | 0.3536481 | putative oxygenase (putative secreted protein) |
| calcium-dependent_antibiotic|4|50_1|Scoe | 953 | 0.4233161 | 817 | 136 | 1.166463 | 0.1427072 | FIG01125970: hypothetical protein |
| calcium-dependent_antibiotic|4|51_1|Scoe | 904 | 0.3968912 | 766 | 138 | 1.180157 | 0.1526549 | FIG01122924: hypothetical protein |
| calcium-dependent_antibiotic|4|52_1|Scoe | 959 | 0.4243523 | 819 | 140 | 1.170940 | 0.1459854 | FIG01124815: hypothetical protein |
| calcium-dependent_antibiotic|4|53_1|Scoe | 893 | 0.4046632 | 781 | 112 | 1.143406 | 0.1254199 | FIG01127693: hypothetical protein |
| calcium-dependent_antibiotic|4|54_1|Scoe | 1070 | 0.4398964 | 849 | 221 | 1.260306 | 0.2065421 | putaive isomerase |
| calcium-dependent_antibiotic|4|55_1|Scoe | 865 | 0.3549223 | 685 | 180 | 1.262774 | 0.2080925 | FIG00557539: hypothetical protein |
| calcium-dependent_antibiotic|4|56_1|Scoe | 2610 | 0.8554404 | 1651 | 959 | 1.580860 | 0.3674330 | Inositol-1-phosphate synthase (EC 5.5.1.4) |
| calcium-dependent_antibiotic|4|57_1|Scoe | 65 | 0.0316062 | 61 | 4 | 1.065574 | 0.0615385 | secreted protein |
| calcium-dependent_antibiotic|4|58_1|Scoe | 13881 | 0.8352332 | 1612 | 12269 | 8.611042 | 0.8838700 | Salicylate hydroxylase (EC 1.14.13.1) |
| calcium-dependent_antibiotic|4|59_1|Scoe | 6332 | 0.8777202 | 1694 | 4638 | 3.737899 | 0.7324700 | 3-oxoacyl-[acyl-carrier-protein] synthase, KASIII (EC 2.3.1.180) |
| calcium-dependent_antibiotic|4|60_1|Scoe | 6263 | 0.8248705 | 1592 | 4671 | 3.934045 | 0.7458087 | FIG01132699: hypothetical protein |
| calcium-dependent_antibiotic|4|61_1|Scoe | 25611 | 0.9139896 | 1764 | 23847 | 14.518707 | 0.9311233 | 3-oxoacyl-[acyl-carrier-protein] synthase, KASII (EC 2.3.1.41) |
| calcium-dependent_antibiotic|4|62_1|Scoe | 92 | 0.0461140 | 89 | 3 | 1.033708 | 0.0326087 | Acyl carrier protein |
| coelibactin|13|162_1|Scoe | 21980 | 0.9290155 | 1793 | 20187 | 12.258784 | 0.9184258 | 2,3-dihydroxybenzoate-AMP ligase (EC 2.7.7.58) |
| coelibactin|13|163_1|Scoe | 64111 | 0.8238342 | 1590 | 62521 | 40.321384 | 0.9751993 | iron aquisition yersiniabactin synthesis enzyme (Irp2) |
| coelibactin|13|164_1|Scoe | 65475 | 0.8279793 | 1598 | 63877 | 40.973091 | 0.9755937 | Siderophore biosynthesis non-ribosomal peptide synthetase modules |
| coelibactin|13|165_1|Scoe | 475 | 0.2119171 | 409 | 66 | 1.161369 | 0.1389474 | Putative reductoisomerase in siderophore biosynthesis gene cluster |
| coelibactin|13|166_1|Scoe | 542 | 0.1979275 | 382 | 160 | 1.418848 | 0.2952030 | Thiazolinyl imide reductase in siderophore biosynthesis gene cluster |
| coelibactin|13|167_1|Scoe | 20005 | 0.8191710 | 1581 | 18424 | 12.653384 | 0.9209698 | putative cytochrome P450 hydroxylase |
| coelibactin|13|168_1|Scoe | 6767 | 0.7352332 | 1419 | 5348 | 4.768851 | 0.7903059 | Thioesterase in siderophore biosynthesis gene cluster |
| coelibactin|13|169_1|Scoe | 399 | 0.1569948 | 303 | 96 | 1.316832 | 0.2406015 | FIG01124013: hypothetical protein |
| coelibactin|13|170_1|Scoe | 22258 | 0.9782383 | 1888 | 20370 | 11.789195 | 0.9151766 | Transport ATP-binding protein CydC |
| coelibactin|13|171_1|Scoe | 21734 | 0.9797927 | 1891 | 19843 | 11.493390 | 0.9129935 | Putative ABC iron siderophore transporter, fused permease and ATPase domains |
| coelibactin|13|172_1|Scoe | 6038 | 0.9538860 | 1841 | 4197 | 3.279739 | 0.6950977 | Anthranilate synthase, aminase component (EC 4.1.3.27) |
| coelichelin|5|63_1|Scoe | 4954 | 0.7849741 | 1515 | 3439 | 3.269967 | 0.6941865 | Polymyxin synthetase PmxB |
| coelichelin|5|64_1|Scoe | 1009 | 0.3424870 | 661 | 348 | 1.526475 | 0.3448959 | putative esterase |
| coelichelin|5|65_1|Scoe | 22382 | 0.9751295 | 1882 | 20500 | 11.892667 | 0.9159146 | ABC transporter transmembrane protein |
| coelichelin|5|66_1|Scoe | 108707 | 0.8212435 | 1585 | 107122 | 68.584858 | 0.9854195 | Siderophore biosynthesis non-ribosomal peptide synthetase modules |
| coelichelin|5|67_1|Scoe | 22313 | 0.9777202 | 1887 | 20426 | 11.824589 | 0.9154305 | FIG01120908: hypothetical protein |
| coelichelin|5|68_1|Scoe | 6181 | 0.7787565 | 1503 | 4678 | 4.112442 | 0.7568355 | iron-siderophore binding lipoprotein |
| coelichelin|5|69_1|Scoe | 20071 | 0.9803109 | 1892 | 18179 | 10.608351 | 0.9057346 | ABC-type Fe3+-siderophore transport system, ATPase component |
| coelichelin|5|70_1|Scoe | 15867 | 0.9419689 | 1818 | 14049 | 8.727723 | 0.8854226 | ABC-type Fe3+-siderophore transport system, permease 2 component |
| coelichelin|5|71_1|Scoe | 15963 | 0.9430052 | 1820 | 14143 | 8.770879 | 0.8859863 | ABC-type Fe3+-siderophore transport system, permease component |
| coelichelin|5|72_1|Scoe | 3871 | 0.8020725 | 1548 | 2323 | 2.500646 | 0.6001033 | Siderophore biosynthesis protein, monooxygenase |
| coelichelin|5|73_1|Scoe | 4767 | 0.9746114 | 1881 | 2886 | 2.534290 | 0.6054122 | formyltransferase |
| coelimycin|10|121_1|Scoe | 16975 | 0.9155440 | 1767 | 15208 | 9.606678 | 0.8959057 | Transcriptional regulator, TetR family |
| coelimycin|10|122_1|Scoe | 2063 | 0.5803109 | 1120 | 943 | 1.841964 | 0.4571013 | A-factor biosynthesis protein AfsA |
| coelimycin|10|123_1|Scoe | 10992 | 0.8569948 | 1654 | 9338 | 6.645707 | 0.8495269 | FIG01122353: hypothetical protein |
| coelimycin|10|124_1|Scoe | 10657 | 0.8886010 | 1715 | 8942 | 6.213994 | 0.8390729 | putative two-component system sensor kinase |
| coelimycin|10|125_1|Scoe | 1837 | 0.7984456 | 1541 | 296 | 1.192083 | 0.1611323 | 2-oxoglutarate oxidoreductase, beta subunit (EC 1.2.7.3) |
| coelimycin|10|126_1|Scoe | 1836 | 0.7948187 | 1534 | 302 | 1.196871 | 0.1644880 | 2-oxoglutarate oxidoreductase, alpha subunit (EC 1.2.7.3) |
| coelimycin|10|127_1|Scoe | 8712 | 0.9611399 | 1855 | 6857 | 4.696496 | 0.7870753 | Biotin carboxylase of acetyl-CoA carboxylase (EC 6.3.4.14) / Biotin carboxyl carrier protein of acetyl-CoA carboxylase |
| coelimycin|10|128_1|Scoe | 4685 | 0.7601036 | 1467 | 3218 | 3.193592 | 0.6868730 | FIG01129816: hypothetical protein |
| coelimycin|10|129_1|Scoe | 40757 | 0.7953368 | 1535 | 39222 | 26.551792 | 0.9623378 | Malonyl CoA-acyl carrier protein transacylase (EC 2.3.1.39) |
| coelimycin|10|130_1|Scoe | 71289 | 0.8010363 | 1546 | 69743 | 46.111902 | 0.9783136 | Malonyl CoA-acyl carrier protein transacylase (EC 2.3.1.39) |
| coelimycin|10|131_1|Scoe | 100940 | 0.7994819 | 1543 | 99397 | 65.418017 | 0.9847137 | Malonyl CoA-acyl carrier protein transacylase (EC 2.3.1.39) |
| coelimycin|10|132_1|Scoe | 2442 | 0.6160622 | 1189 | 1253 | 2.053827 | 0.5131040 | secreted protein |
| coelimycin|10|133_1|Scoe | 17628 | 0.9227979 | 1781 | 15847 | 9.897810 | 0.8989676 | Epoxide hydrolase (EC 3.3.2.9) |
| coelimycin|10|134_1|Scoe | 20004 | 0.9031088 | 1743 | 18261 | 11.476764 | 0.9128674 | Antiseptic resistance protein QacA |
| coelimycin|10|135_1|Scoe | 17612 | 0.9544041 | 1842 | 15770 | 9.561346 | 0.8954122 | Acetylornithine aminotransferase (EC 2.6.1.11) |
| coelimycin|10|136_1|Scoe | 16933 | 0.8155440 | 1574 | 15359 | 10.757942 | 0.9070454 | Cys-tRNA(Pro) deacylase YbaK |
| coelimycin|10|137_1|Scoe | 4447 | 0.7533679 | 1454 | 2993 | 3.058459 | 0.6730380 | secreted FAD-binding protein |
| coelimycin|10|138_1|Scoe | 20000 | 0.9067358 | 1750 | 18250 | 11.428571 | 0.9125000 | 3-oxoacyl-[acyl-carrier protein] reductase (EC 1.1.1.100) |
| coelimycin|10|139_1|Scoe | 8851 | 0.8455959 | 1632 | 7219 | 5.423407 | 0.8156141 | FIG01131835: hypothetical protein |
| coelimycin|10|140_1|Scoe | 9875 | 0.9487047 | 1831 | 8044 | 5.393228 | 0.8145823 | Acetyl-coenzyme A carboxyl transferase alpha chain (EC 6.4.1.2) / Acetyl-coenzyme A carboxyl transferase beta chain (EC 6.4.1.2); Propionyl-CoA carboxylase beta chain (EC 6.4.1.3) |
| coelimycin|10|141_1|Scoe | 11 | 0.0056995 | 11 | 0 | 1.000000 | 0.0000000 | hypothetical protein |
| coelimycin|10|142_1|Scoe | 5128 | 0.6829016 | 1318 | 3810 | 3.890744 | 0.7429797 | FIG01121841: hypothetical protein |
| coelimycin|10|143_1|Scoe | 6893 | 0.7357513 | 1420 | 5473 | 4.854225 | 0.7939939 | Thioesterase in siderophore biosynthesis gene cluster |
| coelimycin|10|144_1|Scoe | 17031 | 0.8170984 | 1577 | 15454 | 10.799620 | 0.9074041 | FIG01136508: hypothetical protein |
| desferrioxamine_B|3|17_1|Scoe | 1647 | 0.6393782 | 1234 | 413 | 1.334684 | 0.2507590 | Putative Desferrioxamine E transporter |
| desferrioxamine_B|3|18_1|Scoe | 5113 | 0.8398964 | 1621 | 3492 | 3.154226 | 0.6829650 | Hypothetical protein associated with desferrioxamine E biosynthesis |
| desferrioxamine_B|3|19_1|Scoe | 4133 | 0.7880829 | 1521 | 2612 | 2.717291 | 0.6319865 | Desferrioxamine E biosynthesis protein DesA @ Siderophore biosynthesis L-2,4-diaminobutyrate decarboxylase |
| desferrioxamine_B|3|20_1|Scoe | 4083 | 0.8103627 | 1564 | 2519 | 2.610614 | 0.6169483 | Desferrioxamine E biosynthesis protein DesB @ Siderophore biosynthesis protein, monooxygenase |
| desferrioxamine_B|3|21_1|Scoe | 2979 | 0.6305699 | 1217 | 1762 | 2.447823 | 0.5914736 | Desferrioxamine E biosynthesis protein DesC @ Siderophore synthetase small component, acetyltransferase |
| desferrioxamine_B|3|22_1|Scoe | 2462 | 0.6580311 | 1270 | 1192 | 1.938583 | 0.4841592 | Desferrioxamine E biosynthesis protein DesD @ Siderophore synthetase superfamily, group C @ Siderophore synthetase component, ligase |
| geosmin|9|120_1|Scoe | 5575 | 0.6326425 | 1221 | 4354 | 4.565930 | 0.7809865 | FIG01124023: hypothetical protein |
| hopene|12|149_1|Scoe | 3685 | 0.8227979 | 1588 | 2097 | 2.320529 | 0.5690638 | Phytoene synthase (EC 2.5.1.32) |
| hopene|12|150_1|Scoe | 3754 | 0.8284974 | 1599 | 2155 | 2.347717 | 0.5740543 | Phytoene synthase (EC 2.5.1.32) |
| hopene|12|151_1|Scoe | 19 | 0.0098446 | 19 | 0 | 1.000000 | 0.0000000 | hypothetical protein |
| hopene|12|152_1|Scoe | 1326 | 0.5943005 | 1147 | 179 | 1.156059 | 0.1349925 | Phytoene desaturase, pro-zeta-carotene producing (EC 1.-.-.-) |
| hopene|12|153_1|Scoe | 7874 | 0.9818653 | 1895 | 5979 | 4.155145 | 0.7593345 | Octaprenyl diphosphate synthase (EC 2.5.1.90); Dimethylallyltransferase (EC 2.5.1.1); (2E,6E)-farnesyl diphosphate synthase (EC 2.5.1.10); Geranylgeranyl pyrophosphate synthetase (EC 2.5.1.29) |
| hopene|12|154_1|Scoe | 1553 | 0.6036269 | 1165 | 388 | 1.333047 | 0.2498390 | Squalene–hopene cyclase (EC 5.4.99.17) |
| hopene|12|155_1|Scoe | 1123 | 0.5673575 | 1095 | 28 | 1.025571 | 0.0249332 | hypothetical protein Bcep3774, commonly clustered with carotenoid biosynthesis |
| hopene|12|156_1|Scoe | 1417 | 0.6321244 | 1220 | 197 | 1.161475 | 0.1390261 | Radical SAM protein required for addition of adenosine to hopane skeleton, HpnH |
| hopene|12|157_1|Scoe | 2606 | 0.9549223 | 1843 | 763 | 1.413999 | 0.2927859 | 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase (EC 1.17.7.1) |
| hopene|12|158_1|Scoe | 8746 | 0.9766839 | 1885 | 6861 | 4.639788 | 0.7844729 | 1-deoxy-D-xylulose 5-phosphate synthase (EC 2.2.1.7) |
| hopene|12|159_1|Scoe | 20012 | 0.9580311 | 1849 | 18163 | 10.823148 | 0.9076054 | Aminotransferase HpnO, required for aminobacteriohopanetriol |
| hopene|12|160_1|Scoe | 6824 | 0.8357513 | 1613 | 5211 | 4.230626 | 0.7636284 | putative DNA-binding protein |
| hopene|12|161_1|Scoe | 650 | 0.3290155 | 635 | 15 | 1.023622 | 0.0230769 | hypothetical protein |
| melanin|2|15_1|Scoe | 1379 | 0.4336788 | 837 | 542 | 1.647551 | 0.3930384 | tyrosinase (monophenol monooxygenase) |
| melanin|2|16_1|Scoe | 1180 | 0.3735751 | 721 | 459 | 1.636616 | 0.3889831 | tyrosinase co-factor |
| methylenomycin|14|173_1|Scoe | 7813 | 0.8538860 | 1648 | 6165 | 4.740898 | 0.7890695 | NADH-FMN oxidoreductase |
| methylenomycin|14|174_1|Scoe | 1056 | 0.4051813 | 782 | 274 | 1.350384 | 0.2594697 | hypothetical protein |
| methylenomycin|14|175_1|Scoe | 10511 | 0.8020725 | 1548 | 8963 | 6.790052 | 0.8527257 | DNA-binding protein |
| methylenomycin|14|176_1|Scoe | 4408 | 0.8056995 | 1555 | 2853 | 2.834727 | 0.6472323 | Predicted dinucleotide-binding enzymes |
| methylenomycin|14|177_1|Scoe | 8190 | 0.8844560 | 1707 | 6483 | 4.797891 | 0.7915751 | 2,4-dienoyl-CoA reductase [NADPH] (EC 1.3.1.34) |
| methylenomycin|14|178_1|Scoe | 128 | 0.0616580 | 119 | 9 | 1.075630 | 0.0703125 | AvrD protein |
| methylenomycin|14|179_1|Scoe | 134 | 0.0507772 | 98 | 36 | 1.367347 | 0.2686567 | putative ATP/GTP-binding protein, MmyX |
| methylenomycin|14|180_1|Scoe | 6097 | 0.8777202 | 1694 | 4403 | 3.599174 | 0.7221584 | 3-oxoacyl-[acyl-carrier-protein] synthase, KASIII (EC 2.3.1.180) |
| methylenomycin|14|181_1|Scoe | 477 | 0.2046632 | 395 | 82 | 1.207595 | 0.1719078 | putative acyl carrier protein, MmyA |
| methylenomycin|14|182_1|Scoe | 3944 | 0.9202073 | 1776 | 2168 | 2.220721 | 0.5496957 | Phosphoserine phosphatase |
| methylenomycin|14|183_1|Scoe | 135 | 0.0507772 | 98 | 37 | 1.377551 | 0.2740741 | putative ATP/GTP-binding protein, MmyX |
| methylenomycin|14|184_1|Scoe | 20001 | 0.9010363 | 1739 | 18262 | 11.501438 | 0.9130543 | Permeases of the major facilitator superfamily |
| methylenomycin|14|185_1|Scoe | 3166 | 0.7025907 | 1356 | 1810 | 2.334808 | 0.5716993 | Transcriptional regulator, ArsR family |
| methylenomycin|14|186_1|Scoe | 8669 | 0.9165803 | 1769 | 6900 | 4.900509 | 0.7959396 | putative oxidoreductase |
| methylenomycin|14|187_1|Scoe | 11630 | 0.8746114 | 1688 | 9942 | 6.889810 | 0.8548581 | Limonene 1,2-monooxygenase |
| methylenomycin|14|188_1|Scoe | 4156 | 0.6854922 | 1323 | 2833 | 3.141345 | 0.6816651 | Thioesterase |
| methylenomycin|14|189_1|Scoe | 20016 | 0.9466321 | 1827 | 18189 | 10.955665 | 0.9087230 | Transcriptional regulator, TetR family |
| methylenomycin|14|190_1|Scoe | 1965 | 0.5689119 | 1098 | 867 | 1.789618 | 0.4412214 | A-factor biosynthesis protein AfsA |
| methylenomycin|14|191_1|Scoe | 3608 | 0.6279793 | 1212 | 2396 | 2.976898 | 0.6640798 | Pigment protein |
| methylenomycin|14|192_1|Scoe | 3716 | 0.9165803 | 1769 | 1947 | 2.100622 | 0.5239505 | Phosphoserine phosphatase |
| methylenomycin|14|193_1|Scoe | 8099 | 0.8637306 | 1667 | 6432 | 4.858428 | 0.7941721 | Transcriptional regulator MmyR, TetR family |
| sapB|11|145_1|Scoe | 5358 | 0.7549223 | 1457 | 3901 | 3.677419 | 0.7280702 | Lanthionine biosynthesis protein LanL |
| sapB|11|146_1|Scoe | 361 | 0.1818653 | 351 | 10 | 1.028490 | 0.0277008 | Lanthionine precursor peptide LanA |
| sapB|11|147_1|Scoe | 22078 | 0.9792746 | 1890 | 20188 | 11.681482 | 0.9143944 | FIG01133883: hypothetical protein |
| sapB|11|148_1|Scoe | 21810 | 0.9782383 | 1888 | 19922 | 11.551907 | 0.9134342 | FIG01121693: hypothetical protein |
| SCO-2138|1|1_1|Scoe | 2435 | 0.6227979 | 1202 | 1233 | 2.025790 | 0.5063655 | FIG01129357: hypothetical protein |
| SCO-2139|1|2_1|Scoe | 2390 | 0.7010363 | 1353 | 1037 | 1.766445 | 0.4338912 | Gluconolactonase (EC 3.1.1.17) |
| SCO-2140|1|3_1|Scoe | 17246 | 0.9316062 | 1798 | 15448 | 9.591769 | 0.8957439 | Transcriptional regulator, IclR family |
| SCO-2141|1|4_1|Scoe | 915 | 0.4621762 | 892 | 23 | 1.025785 | 0.0251366 | FIG01121703: hypothetical protein |
| SCO-2142|1|5_1|Scoe | 19837 | 0.9445596 | 1823 | 18014 | 10.881514 | 0.9081010 | Transcriptional regulator, GntR family |
| SCO-2143|1|6_1|Scoe | 816 | 0.2559585 | 494 | 322 | 1.651822 | 0.3946078 | Dicarboxylate carrier protein |
| SCO-2144|1|7_1|Scoe | 23060 | 0.9461140 | 1826 | 21234 | 12.628697 | 0.9208153 | putative fatty acid synthase |
| SCO-2145|1|8_1|Scoe | 7619 | 0.9331606 | 1801 | 5818 | 4.230428 | 0.7636173 | Acetyl-coenzyme A carboxyl transferase alpha chain (EC 6.4.1.2) / Acetyl-coenzyme A carboxyl transferase beta chain (EC 6.4.1.2) |
| SCO-2146|1|9_1|Scoe | 16284 | 0.8663212 | 1672 | 14612 | 9.739234 | 0.8973225 | putative secreted peptidase |
| SCO-2147|1|10_1|Scoe | 782 | 0.2829016 | 546 | 236 | 1.432234 | 0.3017903 | FIG01131749: hypothetical protein |
| SCO-2148|1|11_1|Scoe | 577 | 0.2227979 | 430 | 147 | 1.341860 | 0.2547660 | hypothetical protein |
| SCO-2149|1|12_1|Scoe | 3052 | 0.7217617 | 1393 | 1659 | 2.190955 | 0.5435780 | MoxR-like ATPases |
| SCO-2150|1|13_1|Scoe | 20140 | 0.9455959 | 1825 | 18315 | 11.035616 | 0.9093843 | FIG01122502: hypothetical protein |
| SCO-2151|1|14_1|Scoe | 2854 | 0.6896373 | 1331 | 1523 | 2.144252 | 0.5336370 | Rod shape-determining protein MreB |
| undecylprodigiosin|8|100_1|Scoe | 20004 | 0.8865285 | 1711 | 18293 | 11.691408 | 0.9144671 | Butyryl-CoA dehydrogenase (EC 1.3.99.2) |
| undecylprodigiosin|8|101_1|Scoe | 65 | 0.0336788 | 65 | 0 | 1.000000 | 0.0000000 | RedY protein |
| undecylprodigiosin|8|102_1|Scoe | 20000 | 0.8974093 | 1732 | 18268 | 11.547344 | 0.9134000 | two-component system response regulator |
| undecylprodigiosin|8|103_1|Scoe | 67 | 0.0341969 | 66 | 1 | 1.015151 | 0.0149254 | RedV protein |
| undecylprodigiosin|8|104_1|Scoe | 120 | 0.0611399 | 118 | 2 | 1.016949 | 0.0166667 | FIG01126548: hypothetical protein |
| undecylprodigiosin|8|105_1|Scoe | 50 | 0.0259067 | 50 | 0 | 1.000000 | 0.0000000 | hypothetical protein |
| undecylprodigiosin|8|106_1|Scoe | 26 | 0.0134715 | 26 | 0 | 1.000000 | 0.0000000 | hypothetical protein |
| undecylprodigiosin|8|107_1|Scoe | 25705 | 0.9145078 | 1765 | 23940 | 14.563739 | 0.9313363 | 3-oxoacyl-[acyl-carrier-protein] synthase, KASII (EC 2.3.1.41) |
| undecylprodigiosin|8|108_1|Scoe | 912 | 0.3362694 | 649 | 263 | 1.405239 | 0.2883772 | Acyl carrier protein |
| undecylprodigiosin|8|109_1|Scoe | 6755 | 0.8777202 | 1694 | 5061 | 3.987603 | 0.7492228 | 3-oxoacyl-[acyl-carrier-protein] synthase, KASIII (EC 2.3.1.41) |
| undecylprodigiosin|8|110_1|Scoe | 200 | 0.0979275 | 189 | 11 | 1.058201 | 0.0550000 | Acyl carrier protein |
| undecylprodigiosin|8|111_1|Scoe | 4155 | 0.8362694 | 1614 | 2541 | 2.574349 | 0.6115523 | Aminotransferase class II, serine palmitoyltransferase like (EC 2.3.1.50) |
| undecylprodigiosin|8|112_1|Scoe | 35354 | 0.8388601 | 1619 | 33735 | 21.836936 | 0.9542060 | non-ribosomal peptide synthetase |
| undecylprodigiosin|8|113_1|Scoe | 29318 | 0.8492228 | 1639 | 27679 | 17.887736 | 0.9440958 | Capsular polysaccharide biosynthesis fatty acid synthase WcbR |
| undecylprodigiosin|8|114_1|Scoe | 12082 | 0.9331606 | 1801 | 10281 | 6.708495 | 0.8509353 | probable oxidoreductase |
| undecylprodigiosin|8|115_1|Scoe | 6650 | 0.7378238 | 1424 | 5226 | 4.669944 | 0.7858647 | putative thioesterase |
| undecylprodigiosin|8|116_1|Scoe | 2639 | 0.7170984 | 1384 | 1255 | 1.906792 | 0.4755589 | putative methyltransferase |
| undecylprodigiosin|8|117_1|Scoe | 3142 | 0.6393782 | 1234 | 1908 | 2.546191 | 0.6072565 | Pyruvate-utilizing enzyme, similar to phosphoenolpyruvate synthase |
| undecylprodigiosin|8|118_1|Scoe | 3303 | 0.7129534 | 1376 | 1927 | 2.400436 | 0.5834090 | Rieske (2Fe-2S) domain protein |
| undecylprodigiosin|8|119_1|Scoe | 673 | 0.3212435 | 620 | 53 | 1.085484 | 0.0787519 | FIG01125690: hypothetical protein |
| undecylprodigiosin|8|98_1|Scoe | 17096 | 0.8160622 | 1575 | 15521 | 10.854603 | 0.9078732 | FIG01131857: hypothetical protein |
| undecylprodigiosin|8|99_1|Scoe | 47731 | 0.8601036 | 1660 | 46071 | 28.753615 | 0.9652218 | FIG01134662: hypothetical protein |
PResence Absence EvoMining was run over enzymes with expansion number between .1 and .6
Figure 4 Pan cluster Idea on closed Streptomyces
Open /closed coelicolor How spread is the cluster
Took 15 clusters from Streptomyces coelicolor on MiBig Analize its open/close pancluster according to EvoMining backwards
O sea 15 corasones, no necesito escoger las query enzyme, al menos 3 por cluster… y que no sean NRPS o PKS
MEthodology
[@dufresne_algorithmique_2016,@blin_recent_nodate,@kurtboke_revisiting_2017,@miller_interpreting_2017,@schniete_expanding_2017,@kim_recent_2017,@robertsen_toward_2017,@juarez-vazquez_evolution_nodate,@chavali_bioinformatics_nodate,@tracanna_mining_2017,@ren_breaking_2017,@choudhary_current_2017,@alanjary_antibiotic_2017,@chevrette_sandpuma:_2017,@wohlleben_antibiotic_2016,@weber_secondary_2016]References
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